1. Field of Invention
The present invention relates to high purity associated complexes of a phospholipid (PL) and a selective and/or nonselective non-steroidal, anti-inflammatory drug (sns-NSAID) and to methods for making and using same. The present invention also relates to method for screening compounds including pharmaceutical agents (PA) for either ability to increase the solubility of a phospholipid (PL) in a solvent in which the PL has a moderate solubility, has a low solubility or is insoluble.
More particularly, the present invention relates to high purity associated complexes of a phospholipid (PL) and a selective and/or nonselective non-steroidal, anti-inflammatory drug and to methods for making and using same, where the complexes comprise polar solvent soluble, PL-sns-NSAID complexes. The method includes the steps of adding a selective and/or nonselective non-steroidal, anti-inflammatory drug (sns-NSAID) and a phospholipid (PL) to a polar solvent and then removing the polar solvent with or without cooling in the presence or absence of a vacuum to form the purified PL-sns-NSAID associated complexes. The present invention also relates to method for screening pharmaceutical agents (PAs) including adding the PA to a solvent in which the PL has a moderate solubility, has a low solubility or is insoluble and then adding a PL to determine whether the solubility of the PL is increased.
2. Description of Related Art
Phospholipids are known to associate with pharmaceutical agents such as selective and nonselective nonsteroidal anti-inflammatory drugs (sns-NSAIDs which include NSAIDs and/or COX-2 inhibitors) that are well known to be associated with gastrointestinal (GI), hepatic and renal adverse side effects, with gastroduodenal ulceration and bleeding being most common and tend to reduce if not eliminate these adverse health risks.
The following Foreign Patents, United States Patents and United States Pending Patent Applications set the prior art relevant to this application: GB 0092121, U.S. Pat. No. 4,332,795; U.S. Pat. No. 4,369,182; U.S. Pat. No. 4,378,354; U.S. Pat. No. 4,421,747; U.S. Pat. No. 4,528,193; U.S. Pat. No. 4,687,766; U.S. Pat. No. 4,748,157; U.S. Pat. No. 4,918,063; U.S. Pat. No. 4,950,656; U.S. Pat. No. 5,032,585; U.S. Pat. No. 5,043,329; U.S. Pat. No. 5,763,422; U.S. Pat. No. 5,955,451; U.S. Ser. No. 10/433,454; U.S. Ser. No. 10/909,748, and U.S. Ser. No. 10/909,751, incorporated herein by reference. These references demonstrated that phospholipids can reduce or eliminate the GI toxicity of the NSAIDs.
Although phospholipids are known to reduce the GI toxicity of NSAIDs and to form associated complexes, there is a need in the art for high purity PL-sns-NSAID associated complexes, for method for making and using same. There is also a need in the art for methods for screening pharmaceutical agents that can form associated complexes with phospholipids.